Biological component collection system and circuit internal pressure acquisition method

ABSTRACT

A biological component collection system and a circuit internal pressure acquisition method are provided, which are capable of accurately measuring the circuit internal pressure. A centrifugal separation device of a blood component collection system comprises an estimated data calculation unit that calculates estimated data B on the basis of initial data A, and a correction unit that corrects the estimated data B in a manner so that the internal pressure calculated by a first internal pressure calculation unit becomes equivalent to the internal pressure calculated by a second internal pressure calculation unit.

TECHNICAL FIELD

The present invention relates to a biological component collectionsystem equipped with a biological component collection device configuredto be attachable to a separation device, as well as to a circuitinternal pressure acquisition method.

BACKGROUND ART

In blood donation in recent years, in addition to whole blood collectionin which whole blood is collected from blood donors, component bloodsampling (apheresis) has been performed in which the burden on the blooddonor's body is made lighter. Component blood sampling is a bloodcollection method in which a blood component collection system(apheresis system) is used, whereby only specific blood components arecollected from whole blood, and the remaining blood components arereturned again into the donor's body.

In Patent Document 1, a blood component collection system is disclosedin which blood platelets are collected by centrifugally separating wholeblood that is extracted from a blood donor. Such a blood componentcollection system comprises a blood collection circuit set, which formsa circuit through which blood or blood components to be treated flow,and a centrifugal separation device (blood component separation device)in which the blood collection circuit set is mounted.

The blood collection circuit set is equipped with a plurality of bagsfor accommodating a blood collection line having a blood collectionneedle, a band-shaped channel (separator) into which whole blood isintroduced, and the blood components, etc., and a cassette connectedthrough a plurality of tubes to the bags. A plurality of flow paths,including a line for introducing blood from a blood donor, a line fortransferring the blood components into a bag, a blood returning line forreturning uncollected blood components to the donor, etc., are formed inthe cassette. When used, the cassette is mounted in a mounting unitdisposed in the blood component separation device.

PRIOR ART DOCUMENTS Patent Document 1

Published Japanese Translation of PCT International Application No.2013-514863 (WO2011/084348).

SUMMARY OF INVENTION Problems the Invention Aims to Solve

In such a blood component collection system, in order to ascertainwhether or not the blood component separation device is operatingproperly, it is necessary to measure and monitor the pressure (circuitinternal pressure) inside the blood collection circuit. Similar problemsalso occur in biological component collection systems other than bloodcomponent collection systems.

The present invention has been devised taking into consideration theaforementioned problems, and has the object of providing a biologicalcomponent collection system and a circuit internal pressure acquisitionmethod, which are capable of accurately measuring the circuit internalpressure.

Means for Solving the Problem

One aspect of the present invention relates to a biological componentcollection system equipped with a separation device adapted to separatea biological component from a biological liquid, a biological componentcollection device configured to be attachable to the separation deviceand having a biological liquid line formed therein through which thebiological liquid or the biological component flows, and a collectionand returning pump, the biological component collection systemperforming a collection operation for collecting a desired biologicalcomponent in the biological liquid by allowing the biological liquid toflow from a donor through the biological liquid line to the separationdevice under an action of the collection and returning pump, and areturning operation for returning remaining biological components to thedonor from the separation device through the biological liquid lineunder the action of the collection and returning pump, wherein thebiological component collection device is formed of a soft material andhas a line forming member defining the biological liquid line, and theseparation device comprises a first load detecting unit adapted todetect a load applied to a first applied load measurement unit whichpartially makes up the line forming member in a device installed statein which the biological component collection device is attached to theseparation device, a second load detecting unit adapted to detect a loadapplied to a second applied load measurement unit which partially makesup the line forming member in the device installed state, a dataacquisition unit adapted to acquire, before the biological liquid or thebiological component is made to flow through the biological liquid linefor biological component collection, initial data indicative of atimewise change in a reaction force of the first applied loadmeasurement unit using the load detected by the first load detectingunit in the device installed state, an estimated data calculation unitadapted to calculate, on the basis of the initial data, estimated datafor estimating the reaction force of the first applied load measurementunit which changes depending on time during collection of the biologicalcomponent, a reaction force calculation unit adapted to calculate,during collection of the biological component, the reaction force on thebasis of the estimated data, a first internal pressure calculation unitadapted to calculate an internal pressure of the first applied loadmeasurement unit on the basis of the reaction force calculated by thereaction force calculation unit and the load detected by the first loaddetecting unit, a second internal pressure calculation unit adapted tocalculate an internal pressure of the second applied load measurementunit on the basis of the load detected by the second load detectingunit, and a correction unit adapted to correct the estimated data in amanner so that the internal pressure calculated by the first internalpressure calculation unit becomes equivalent to the internal pressurecalculated by the second internal pressure calculation unit, at a timebetween the collection operation and the returning operation, in a statein which an inner hole of the first applied load measurement unit and aninner hole of the second applied load measurement unit communicate witheach other and the collection and returning pump is stopped.

Another aspect of the present invention relates to a circuit internalpressure acquisition method using a biological component collectionsystem equipped with a separation device adapted to separate abiological component from a biological liquid, a biological componentcollection device configured to be attachable to the separation deviceand having a biological liquid line formed therein through which thebiological liquid or the biological component flows, and a collectionand returning pump, the biological component collection systemperforming a collection operation for collecting a desired biologicalcomponent in the biological liquid by allowing the biological liquid toflow from a donor through the biological liquid line to the separationdevice under an action of the collection and returning pump, and areturning operation for returning remaining biological components to thedonor from the separation device through the biological liquid lineunder the action of the collection and returning pump, wherein thebiological component collection device is formed of a soft material andhas a line forming member defining the biological liquid line, and theseparation device comprises a first load detecting unit adapted todetect a load applied to a first applied load measurement unit whichpartially makes up the line forming member in a device installed statein which the biological component collection device is attached to theseparation device, and a second load detecting unit adapted to detect aload applied to a second applied load measurement unit which partiallymakes up the line forming member in the device installed state, thecircuit internal pressure acquisition method comprising a dataacquisition step of acquiring, before the biological liquid or thebiological component is made to flow through the biological liquid linefor biological component collection, initial data indicative of atimewise change in a reaction force of the first applied loadmeasurement unit using the load detected by the first load detectingunit in the device installed state, an estimated data calculation stepof calculating on the basis of the initial data, estimated data forestimating the reaction force of the first applied load measurement unitwhich changes depending on time during collection of the biologicalcomponent, a reaction force calculation step of calculating, duringcollection of the biological component, the reaction force on the basisof the estimated data, a first internal pressure calculation step ofcalculating an internal pressure of the first applied load measurementunit on the basis of the reaction force calculated in the reaction forcecalculation step and the load detected by the first load detecting unit,a second internal pressure calculation step of calculating an internalpressure of the second applied load measurement unit on the basis of theload detected by the second load detecting unit, and a correction stepof correcting the estimated data in a manner so that the internalpressure calculated in the first internal pressure calculation stepbecomes equivalent to the internal pressure calculated in the secondinternal pressure calculation step, at a time between the collectionoperation and the returning operation, and in a state in which thecollection and returning pump is stopped.

EFFECTS OF THE INVENTION

According to the present invention, since based on the estimated data itis possible to calculate the reaction force of the first applied loadmeasurement unit which changes with the passage of time duringcollection of biological components, it is possible for the circuitinternal pressure to be accurately measured. Further, since theestimated data is corrected in a manner so that the internal pressurecalculated by the first internal pressure calculation unit becomesequivalent to the internal pressure calculated by the second internalpressure calculation unit at a time between the collection operation andthe returning operation, the circuit internal pressure can be measuredmore accurately.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic diagram of a blood component collection systemaccording to an embodiment of the present invention;

FIG. 2 is a perspective view of a blood component collection cassette;

FIG. 3 is a perspective view of a cassette mounting unit;

FIG. 4 is a perspective view of a cassette mounting unit in a state withthe blood component collection cassette placed therein;

FIG. 5 is a first explanatory diagram illustrating the operation ofclamps;

FIG. 6 is a second explanatory diagram illustrating the operation ofclamps;

FIG. 7 is a third explanatory diagram illustrating the operation ofclamps;

FIG. 8 is a fourth explanatory diagram illustrating the operation ofclamps;

FIG. 9 is a fifth explanatory diagram illustrating the operation ofclamps;

FIG. 10 is a first flowchart for describing a circuit internal pressureacquisition method according to an embodiment of the present invention;

FIG. 11 is a second flowchart for describing a circuit internal pressureacquisition method according to an embodiment of the present invention;

FIG. 12 is a graph for describing estimated data;

FIG. 13 is a graph for describing a correction to the slope of acalibration curve;

FIG. 14 is an explanatory diagram for explaining a state in which aninner hole of a first applied load measurement unit and an inner hole ofa second applied load measurement unit are in communication with eachother;

FIG. 15 is a graph for describing a correction step;

FIG. 16A is a diagram for describing load detection at a positivepressure;

FIG. 16B is a diagram for describing load detection at a negativepressure; and

FIG. 17 is a graph for describing a timewise change in a reaction force.

DESCRIPTION OF EMBODIMENTS

Preferred embodiments of a biological component collection system and acircuit internal pressure acquisition method according to the presentinvention will be presented and described in detail below with referenceto the accompanying drawings.

As shown in FIG. 1, a blood component collection system 10, which is oneform of a biological component collection system according to thepresent invention, is constituted as a blood apheresis system, in whichblood (whole blood) is continuously extracted from a blood donor andsubjected to centrifugal separation outside the body, whereby a specificblood component (in the present embodiment, plasma (platelet poorplasma: PPP)) is collected, and the remaining blood components arereturned to the blood donor. In the present embodiment, the bloodcomponent is a biological component, and the blood is a biologicalliquid (a liquid containing at least one biological component).

First, an outline description will be given of the blood componentcollection system 10 shown in FIG. 1. The blood component collectionsystem 10 is equipped with a blood collection circuit set 12 forenabling storage and flow of blood components therein, and a centrifugalseparation device 14 (separation device) that applies a centrifugalforce to the blood collection circuit set 12. The blood collectioncircuit set 12 includes a blood treatment unit 16 (biological liquidtreatment unit) in which whole blood that is removed from the blooddonor is centrifugally separated into a plurality of blood components.The centrifugal separation device 14 is equipped with a centrifuge unit18 having a rotor 18 a for applying a centrifugal force to the bloodtreatment unit 16. The blood treatment unit 16 is capable of beingmounted in the centrifuge unit 18.

The blood collection circuit set 12 is discarded every time that it isused in order to prevent contamination and ensure sanitation. The bloodcollection circuit set 12 includes a blood collection and bloodreturning unit 22 having a blood collecting needle 20 and an initialflow blood collecting bag 21, the blood treatment unit 16, a pluralityof bags 24, and a blood component collection cassette 28 (hereinafterreferred to as a “cassette 28”) serving as a biological componentcollection device to which the aforementioned elements are connected viatubes. The plurality of bags 24 include an ACD solution bag 24 acontaining an ACD solution which is an anticoagulant, and a PPP bag 24 bfor storing the plasma (platelet poor plasma).

The blood collection and blood returning unit 22 is connected to the ACDsolution bag 24 a and the cassette 28 via a tube connector 30. The ACDsolution bag 24 a is connected to the tube connector 30 via an ACDsolution transfer tube 23.

The cassette 28 is connected to the blood collection and blood returningunit 22 via a donor side tube 32, and is also connected to the bloodtreatment unit 16 via a treatment unit side tube 34. The blood treatmentunit 16 is attached to the centrifuge unit 18 (rotor 18 a) of thecentrifugal separation device 14, and is configured in the form of acontainer in which blood can be introduced therein, flow therethrough,and flow out therefrom. The PPP bag 24 b is connected to the bloodtreatment unit 16 via a PPP transfer tube 36.

As shown in FIG. 2, the cassette 28 is provided with a cassette body 40in which a blood line 42 (biological liquid line) is formed throughwhich blood or blood components flow. The cassette body 40 is formed ina rectangular shape as viewed in plan. The cassette body 40 is formed ofa soft material. For the soft material that constitutes the cassettebody 40, the same material is used over the entirety of the cassettebody 40. Moreover, the cassette body 40 may be constituted from aplurality of different materials. More specifically, the cassette body40 includes a first sheet 40 a and a second sheet 40 b formed of a softmaterial. The first sheet 40 a and the second sheet 40 b are stacked ina thickness direction and are joined to each other.

As examples of the soft material that constitutes the first sheet 40 aand the second sheet 40 b, there may be cited vinyl chloride,polyolefin, polyurethane, and the like. As examples of a vinyl chlorideplasticizer, there may be cited diisononylcyclohexane-1,2-dicarboxylate,bis-2-ethylhexyl phthalate, and the like.

The blood line 42 is formed between the first sheet 40 a and the secondsheet 40 b. In the present embodiment, fusion bonding (high frequencyfusion bonding, thermal fusion bonding, etc.) is used as the means forjoining the first sheet 40 a and the second sheet 40 b. The first sheet40 a and the second sheet 40 b may also be joined together by anotherjoining means (adhesion or the like). Further, a first port member 44and a second port member 46, which are made of a hard material (forexample, polypropylene, polycarbonate, or the like), are disposed on anouter peripheral edge portion 40 c of the cassette body 40.

The first port member 44 is provided at a first end portion 45 a, whichis one longitudinal end portion of the rectangular cassette body 40, andis connected to a first port 43 a provided on one end side of the bloodline 42. The second port member 46 is provided at a second end portion45 b, which is another longitudinal end portion of the cassette body 40,and is connected to a second port 43 b provided on the other end side ofthe blood line 42. The donor side tube 32 is connected to the first portmember 44, and the treatment unit side tube 34 is connected to thesecond port member 46.

According to the present embodiment, the first port member 44 and thesecond port member 46 are arranged on the same straight line along thelongitudinal direction of the rectangular cassette body 40. It should benoted that the first port member 44 and the second port member 46 neednot necessarily be arranged on the same straight line.

The blood line 42 which is formed in the cassette body 40 includes ablood collection line 42 a (collection line) through which the blood ismade to flow at a time of blood collection, and a blood returning line42 b (returning line) through which the blood components are made toflow at a time that the blood is returned. One end portion 42 a 1 of theblood collection line 42 a and one end portion 42 b 1 of the bloodreturning line 42 b are connected mutually via a first coupling member48. Another end portion 42 a 2 of the blood collection line 42 a andanother end portion 42 b 2 of the blood returning line 42 b areconnected mutually via a second coupling member 50.

The blood collection line 42 a and the blood returning line 42 b extendat least partially in parallel with each other. The first couplingmember 48 and the second coupling member 50 each constitute parts of theblood line 42.

In the cassette body 40, sealed portions 55 in the form of fusion-bondedlocations are formed along the blood line 42 on both sides of the bloodline 42. Further, a sealed portion 57 is formed along the outerperipheral edge portion 40 c, on the outer peripheral edge portion 40 cof the cassette body 40. In the cassette body 40 (excluding the convexportion that forms the blood line 42), locations other than the sealedportions 55 and 57 are non-sealed portions where the first sheet 40 aand the second sheet 40 b are not fusion bonded to each other. Since thesealed portions 55 are subjected to pressure during formation thereof,the sealed portions 55 are smaller in thickness than the non-sealedportions, and are recessed with respect to the non-sealed portions.Stated otherwise, the non-sealed portions protrude in the thicknessdirection with respect to the sealed portions 55.

Within the cassette body 40, even when there is no positive pressureacting within the blood line 42, the wall portions that form the bloodline 42 bulge in convex shapes in the thickness direction of thecassette 28 on both side surfaces of the cassette body 40. Accordingly,the blood line 42 is a flow path which is opened in its natural state.When pressed by an external force, the wall portions can be elasticallydeformed in directions to close the blood line 42 at the pressedlocations thereof.

The cassette body 40 comprises a line forming member 53 that forms theblood line 42. The line forming member 53 includes a first line formingmember 54 that forms the blood collection line 42 a. In the first lineforming member 54, in a cassette attached state (device attached state)in which the cassette 28 is attached to the centrifugal separationdevice 14, a first applied load measurement unit 60 (first pressedportion) is provided, which is pressed by a later-described first loaddetecting unit 88 (see FIG. 3) that is installed in the centrifugalseparation device 14. The first applied load measurement unit 60constitutes a part of the wall portion of the blood collection line 42a. Accordingly, the first applied load measurement unit 60 bulges out inthe thickness direction of the cassette body 40 from a sheet surface 41(base surface) of the cassette body 40.

The line forming member 53 includes a second line forming member 64 thatforms the blood returning line 42 b. In the second line forming member64, in the cassette attached state, a second applied load measurementunit 62 (second pressed portion) is provided, which is pressed by alater-described second load detecting unit 90 (see FIG. 3) that isinstalled in the centrifugal separation device 14. The second appliedload measurement unit 62 constitutes a part of the wall portion of theblood returning line 42 b. Accordingly, the second applied loadmeasurement unit 62 bulges out in the thickness direction of thecassette body 40 from a sheet surface 41 of the cassette body 40.

The second applied load measurement unit 62 constitutes a filteraccommodating unit 65. The filter accommodating unit 65 accommodates afilter member 70 for separating predetermined components (clotted bloodor blood clumps) contained within the blood components.

The second applied load measurement unit 62 is more easily deformablethan the first applied load measurement unit 60. In the presentembodiment, the width of the second applied load measurement unit 62 isgreater than the width of the first applied load measurement unit 60,whereby the second applied load measurement unit 62 is more easilydeformable than the first applied load measurement unit 60. The ratio ofthe width of the second applied load measurement unit 62 with respect tothe width of the first applied load measurement unit 60 is set, forexample, to 300% or greater, preferably is set to 500% or greater, andmore preferably, is set to 800% or greater.

Moreover, the width of the wall portion that constitutes the secondapplied load measurement unit 62 may be set to be thinner than the widthof the wall portion of the first applied load measurement unit 60,whereby the second applied load measurement unit 62 may be more easilydeformable than the first applied load measurement unit 60.Alternatively, the second applied load measurement unit 62 may be madeof a material that is softer than that of the first applied loadmeasurement unit 60, whereby the second applied load measurement unit 62may be more easily deformable than the first applied load measurementunit 60.

On the cassette 28, there are provided a plurality of clamp actionmembers 76 (76 a to 76 c) on which a plurality of clamps 72 (72 a to 72c) (see FIG. 3), which act as flow path opening/closing mechanisms, areprovided in the centrifugal separation device 14. When the cassette 28is installed in the centrifugal separation device 14, the clamp actionmembers 76 abut against or are placed in facing relation to theircorresponding clamps 72. More specifically, the clamp action member 76 ais disposed at a location forming a side of the first port member 44 ofthe blood collection line 42 a in the cassette 28. The clamp actionmembers 76 b, 76 c are disposed respectively at locations forming bothsides of the second applied load measurement unit 62 within the bloodreturning line 42 b.

Moreover, the flow path structure formed in the cassette 28, and thenumber and arrangement of the bags 24 that are provided are not limitedto the configurations shown and described above, but may be modified inaccordance with the type of blood components to be collected, the methodof use, and the like.

In FIG. 1, the centrifugal separation device 14 is a device that is usedrepeatedly during blood component collection, and is provided, forexample, in a medical facility, a blood collection vehicle, or the like.The centrifugal separation device 14 is equipped with the centrifugeunit 18 having the rotor 18 a, and a cassette mounting unit 78configured in a manner so that the cassette 28 of the blood collectioncircuit set 12 is capable of being attached thereto.

As shown in FIG. 3, the cassette mounting unit 78 includes an attachmentbase 84 having a cassette mounting groove 82 formed therein, a lid 86which can be opened and closed and is configured in a manner so as tocover the attachment base 84 when closed, a first load detecting unit 88capable of pressing the first applied load measurement unit 60 (see FIG.2) of the cassette 28, a second load detecting unit 90 capable ofpressing the second applied load measurement unit 62 (see FIG. 2) of thecassette 28, and a plurality of clamps 72 configured to be capable ofpressing the clamp action members 76 (see FIG. 2) of the cassette 28.

A first port arrangement groove 84 b into which the first port member 44of the cassette 28 can be arranged, and a second port arrangement groove84 c into which the second port member 46 of the cassette 28 can bearranged are provided on the outer peripheral portion of the attachmentbase 84. The first port arrangement groove 84 b and the second portarrangement groove 84 c are in communication with the cassette mountinggroove 82.

The lid 86 is connected in a rotatable manner to the attachment base 84via a hinge 85. When the lid 86 is closed with the cassette 28 beingheld in the cassette mounting groove 82 of the attachment base 84, thecassette 28 is sandwiched between the attachment base 84 and the lid 86.On the attachment base 84 and the lid 86, there are respectivelyprovided concave portions 84 a, 86 a in which the filter accommodatingunit 65 of the cassette 28 can be received. Consequently, the cassette28 is appropriately retained between the attachment base 84 and the lid86, while also preventing the filter accommodating unit 65 from beingcrushed. Further, the concave portions 84 a, 86 a prevent the filteraccommodating unit 65 from bulging excessively.

The first load detecting unit 88 is inserted into a first through hole92 a provided in the attachment base 84, together with being exposed inthe cassette mounting groove 82. An upper surface of the first loaddetecting unit 88 protrudes from a bottom surface 82 a of the cassettemounting groove 82. The second load detecting unit 90 is inserted into asecond through hole 92 b provided in a bottom surface 87 of the concaveportion 84 a, together with being exposed in the concave portion 84 a.An upper surface of the second load detecting unit 90 protrudes from thebottom surface 87 of the concave portion 84 a. The first load detectingunit 88 and the second load detecting unit 90 are constituted from loadcells, for example.

The plurality of clamps 72 (72 a to 72 c) are capable of being advancedand retracted in the thickness direction of the cassette 28 in a statein which the cassette 28 is retained in the cassette mounting groove 82,and are disposed corresponding to the arrangement of the plurality ofclamp action members 76 (76 a to 76 c) provided on the cassette 28. Theplurality of clamps 72 are capable of pressing the plurality of clampaction members 76, respectively, via a plurality of holes 94 that openon a bottom surface 82 a of the cassette mounting groove 82. Whenclosed, a plurality of projections 96 are provided on the lid 86 atpositions corresponding to the plurality of holes 94 (clamps 72).

At a time that the clamp action members 76 are not being pressed by theclamps 72, in a state in which the cassette 28 is mounted in thecassette mounting unit 78, the flow paths inside the clamp actionmembers 76 are opened. When the clamps 72 protrude from the holes 94 andpress the clamp action members 76, the flow paths inside the clampaction members 76 are closed. In addition, when the clamps 72 areretracted, due to the elastic restorative force of (the clamp actionmembers 76 of) the cassette body 40, the clamp action members 76 arerestored to their original shape, and the flow paths inside the clampaction members 76 are opened.

As shown in FIG. 1, the centrifugal separation device 14 includes an ACDsolution transfer pump 98 which acts on the ACD solution transfer tube23, and a collection and returning pump 100 which acts on the treatmentunit side tube 34 that is connected to the cassette 28. The ACD solutiontransfer pump 98 is a pump that transfers the ACD solution from the ACDsolution bag 24 a to the cassette 28 and the blood treatment unit 16 viathe ACD solution transfer tube 23. The collection and returning pump 100is a pump for transferring the blood or blood components. Statedotherwise, the collection and returning pump 100 is a pump thattransfers blood from the blood donor to the blood treatment unit 16, andtogether therewith, transfers the blood from the blood treatment unit 16back to the blood donor. The ACD solution transfer pump 98 and thecollection and returning pump 100 are constituted, for example, by aroller pump or a finger pump.

The centrifugal separation device 14 further includes a control unit102. The control unit 102 is a computation device including amicrocomputer, and has a CPU (central processing unit), and a ROM, aRAM, etc., serving as memories, wherein by reading out and executingprograms stored in the ROM, the CPU functions as various functionrealizing units (function realizing means). Moreover, the variousfunction realizing units may be constituted by function realizingdevices in the form of hardware.

The control unit 102 controls operations of the above-describedplurality of clamps 72. The control unit 102 comprises a storage unit104, a data acquisition unit 106, an estimated data calculation unit108, a reaction force calculation unit 110, a first internal pressurecalculation unit 112, a second internal pressure calculation unit 114,and a correction unit 116.

Before collection of blood components during which the blood or bloodcomponents are made to flow in the blood line 42 in the cassetteattached state, the data acquisition unit 106 acquires initial data A(see FIG. 12) indicative of a temporal change in the reaction force ofthe first applied load measurement unit 60. On the basis of the initialdata A, the estimated data calculation unit 108 calculates estimateddata B (see FIG. 12) for the purpose of estimating the reaction force ofthe first applied load measurement unit 60 during collection of theblood components. During collection of the blood components, thereaction force calculation unit 110 calculates the reaction force of thefirst applied load measurement unit 60 based on the estimated data B.

During collection of the blood components, the first internal pressurecalculation unit 112 calculates the internal pressure (circuit internalpressure) of the first applied load measurement unit 60 on the basis ofthe reaction force of the first applied load measurement unit 60 ascalculated by the reaction force calculation unit 110, and the loaddetected by the first load detecting unit 88. During collection of theblood components, the second internal pressure calculation unit 114calculates the internal pressure of the second applied load measurementunit 62 on the basis of the load detected by the second load detectingunit 90.

The correction unit 116 corrects the estimated data B (see FIG. 15) in amanner so that the internal pressure calculated by the first internalpressure calculation unit 112 becomes equivalent to the internalpressure calculated by the second internal pressure calculation unit114, at a time between the collection operation and the returningoperation, in a state in which an inner hole of the first applied loadmeasurement unit 60 and an inner hole of the second applied loadmeasurement unit 62 communicate with each other and the collection andreturning pump 100 is stopped.

Next, operations of the blood component collection system 10 accordingto the present embodiment, which is configured in the manner describedabove, will be described.

As a preparation (set-up) for collecting blood components from a blooddonor using the blood component collection system 10 shown in FIG. 1,the blood collection circuit set 12 is attached to the centrifugalseparation device 14. More specifically, the cassette 28 is mounted inthe cassette mounting unit 78, and the blood treatment unit 16 isattached to the rotor 18 a. On the other hand, the blood collectingneedle 20 pierces and is inserted into the blood donor.

When the cassette 28 is mounted in the cassette mounting unit 78, asshown in FIG. 4, at first, the cassette 28 is mounted in the cassettemounting groove 82. In addition, by closing the lid 86, the cassette 28is placed in a state of being held between the lid 86 and the attachmentbase 84. As a result, the first applied load measurement unit 60 and thesecond applied load measurement unit 62 of the cassette 28 are pressedrespectively by the first load detecting unit 88 and the second loaddetecting unit 90, and are placed in a state of being slightlyelastically deformed. Further, the plurality of clamp action members 76of the cassette 28 are placed in facing relation with respect to theplurality of clamps 72.

When a command is issued by operation of a user with respect to thecentrifugal separation device 14 shown in FIG. 1 in order to initiateoperations, in the centrifugal separation device 14, under the action ofthe ACD solution transfer pump 98, priming with the ACD solution iscarried out. More specifically, at a stage at which it is detected by anon-illustrated line sensor disposed outside of the cassette 28 that theACD solution has arrived in the immediate vicinity of the first port 43a, priming by the ACD solution is terminated.

Next, by rotating the rotor 18 a, the centrifugal separation device 14applies a centrifugal force to the blood treatment unit 16 that isattached to the rotor 18 a, and together therewith, by operation of thecollection and returning pump 100, blood (whole blood) from the blooddonor is extracted and introduced into the blood treatment unit 16(blood collection operation). By the centrifugal force that accompaniesrotation of the rotor 18 a, the blood introduced into the bloodtreatment unit 16 is separated into red blood cells (concentrated redblood cells), a buffy coat, and plasma (platelet poor plasma).

The plasma that is separated in the blood treatment unit 16 isintroduced into the PPP bag 24 b via the PPP transfer tube 36. Aftercompletion of the centrifugal separation process, the remaining bloodcomponents (the red blood cells and the buffy coat) are returned to theblood donor (returning operation). At this time, since foreignsubstances such as blood clumps and the like contained within theremaining blood components are trapped by the filter member 70 providedin the blood returning line 42 b of the cassette 28, any risk of suchforeign matter being returned to the blood donor can be reduced. Thecollection operation and the returning operation described above areperformed a plurality of times.

During operation of the blood component collection system 10, the clamps72 (see FIG. 3) of the centrifugal separation device 14 are operated inthe following manner.

As shown in FIG. 5, when priming by the ACD solution is carried out, theclamps 72 a, 72 b, and 72 c are opened. In addition, in this state,priming by the ACD solution is terminated at a stage at which it isdetected by a non-illustrated line sensor outside the cassette 28 in theimmediate vicinity of the first port 43 a that the ACD solution hasarrived in close proximity to the first port 43 a.

Next, when blood collection is performed for the first time, as shown inFIG. 6, the state in which the clamps 72 a, 72 b, and 72 c are opened ismaintained. In addition, in this state, blood from the blood donor isintroduced into the blood line 42 of the cassette 28, and all of the airinside the circuit of the cassette 28 is pushed out by the blood intothe blood treatment unit 16.

During the course of initial blood collection, as shown in FIG. 7, byclosing the clamps 72 b and 72 c, the blood returning line 42 b isclosed. Consequently, a negative pressure is prevented from acting onthe filter accommodating unit 65 and blocking the filter accommodatingunit 65.

Next, when return of the blood components to the blood donor is carriedout, as shown in FIG. 8, the clamp 72 a is closed, and the clamps 72 band 72 c are opened. Thus, the blood collection line 42 a is closed,whereas the blood returning line 42 b is opened. Accordingly, when theblood components pass through the filter member 70, clotted bloodcontained within the blood components is trapped in the filter member70. Since the blood collection line 42 a is closed, foreign mattercannot be returned to the blood donor via the blood collection line 42a.

Next, when second and subsequent blood collections are carried out, asshown in FIG. 9, the clamps 72 b and 72 c are closed, and the clamp 72 ais opened. Thus, the blood returning line 42 b is closed, whereas theblood collection line 42 a is opened. Accordingly, from among the bloodcollection line 42 a and the blood returning line 42 b, blood istransferred via only the blood collection line 42 a to (the centrifugeunit 18 of) the blood treatment unit 16. Thereafter, return of the blood(see FIG. 8) is carried out again. Collection of blood and return of theblood in this manner are repeated a plurality of times.

In addition, when return of the blood is performed for the last time, asshown in FIG. 8, the clamp 72 a is closed, and the clamps 72 b and 72 care opened.

Next, a circuit internal pressure acquisition method in which the bloodcomponent collection system 10 is used will be described with referenceto the flowcharts shown in FIGS. 10 and 11.

In step S1 of FIG. 10, the control unit 102 determines whether or notthe cassette 28 has been mounted in the cassette mounting unit 78. Morespecifically, the control unit 102 determines that the cassette 28 hasbeen mounted in the cassette mounting unit 78 when the lid 86 is closed,in a state in which the cassette 28 is mounted in the cassette mountinggroove 82 of the attachment base 84.

If the control unit 102 determines that the cassette 28 is not mountedin the cassette mounting unit 78 (step S1: NO), the process remains atstep S1 until it is determined that the cassette 28 has been mounted inthe cassette mounting unit 78.

In the case that the control unit 102 determines that the cassette 28has been mounted in the cassette mounting unit 78 (step S1: YES), thenin step S2, the control unit 102 initiates measurement of an elapsedtime period from when the control unit 102 determines that the cassette28 has been mounted in the cassette mounting unit 78. Subsequently, instep S3, the control unit 102 determines whether or not the elapsed timeperiod has reached the predetermined time period t1 (see FIG. 12). Inthis instance, although the predetermined time period t1 can bearbitrarily set, the predetermined time period t1 may be set to fiveminutes, for example.

If the control unit 102 determines that the elapsed time period has notreached the predetermined time period t1 (step S3: NO), the processremains at step S3 until it is determined that the elapsed time periodhas reached the predetermined time period t1. In the case that thecontrol unit 102 determines that the elapsed time period has reached thepredetermined time period t1 (step S3: YES), then in step S4, a dataacquisition step is performed.

As shown in FIG. 12, in the data acquisition step, before collection ofblood components is performed, the data acquisition unit 106, using theload detected by the first load detecting unit 88 during a predetermineddata acquisition time period t2, acquires the initial data A indicativeof the temporal change in the reaction force of the first applied loadmeasurement unit 60. In this instance, although the predetermined timeperiod t2 can be arbitrarily set, the predetermined time period t2 maybe set to five minutes, for example.

Subsequently, in step S5 of FIG. 10, an estimated data calculation stepis performed. As shown in FIG. 12, in the estimated data calculationstep, on the basis of the initial data A, the estimated data calculationunit 108 calculates estimated data B (a baseline) for the purpose ofestimating the reaction force of the first load detecting unit 88 thatchanges depending on the time period during which the blood componentsare collected. More specifically, the estimated data calculation unit108 calculates the estimated data B using a least squares method basedon the initial data A. Consequently, it is possible to obtain thereaction force of the first applied load measurement unit 60 in realtime, which changes depending on the time period during which the bloodcomponents are collected. The calculated estimated data B is saved(stored) in the storage unit 104.

Next, in the correction step of step S6, the slope of the calibrationcurve L (see FIG. 13), which is data that is used for calculating theinternal pressure, is corrected using the load detected by the secondload detecting unit 90. Consequently, the calibration curve La, theslope of which has been corrected, is obtained. The calibration curve Lcan be acquired in advance by experiment or analysis.

Since the second applied load measurement unit 62 is more easilydeformed than the first applied load measurement unit 60, therelationship between the load detected by the second load detecting unit90 and the pressure corresponding to the load is extremely stable.Accordingly, by using the second load detecting unit 90 as a referencesensor for the first load detecting unit 88, and thereby correcting theslope of the calibration curve L used when calculating the circuitinternal pressure in the correction step, it is possible to measure thecircuit internal pressure with high accuracy.

The correction step may be performed (between step S2 and step S3) untilthe elapsed time period reaches the predetermined time period t1. Inthis case, it is possible to shorten the preparation time until bloodcomponent collection is started.

Subsequently, in step S7 of FIG. 10, the ACD solution transfer pump 98is driven, and carries out the aforementioned priming in which the ACDsolution is filled until immediately before the blood line 42 of thecassette 28. Thereafter, in step S8, blood is introduced into the bloodline 42 of the cassette 28. Stated otherwise, the collection operationis started.

At this time, in step S9 of FIG. 11, the control unit 102 operates thecollection and returning pump 100. Next, in the reaction forcecalculation step of step S10, during collection of the blood components,the reaction force calculation unit 110 calculates the reaction force ofthe first applied load measurement unit 60 based on the estimated data B(see FIG. 12).

In addition, in step S11, during collection of the blood components, thefirst internal pressure calculation unit 112 calculates a differentialload, which is obtained by subtracting the reaction force calculated inthe reaction force calculation step from the load detected by the firstload detecting unit 88, and calculates the internal pressure (circuitinternal pressure) of the first applied load measurement unit 60 on thebasis of the differential load and the calibration curve La, the slopeof which has been corrected.

Thereafter, in step S12, the control unit 102 determines whether or notoperation of the collection and returning pump 100 has been stopped. Thecontrol unit 102 stops operation of the collection and returning pump100 when a predetermined set time period has elapsed from when thecollection operation or the returning operation was started. If it isdetermined by the control unit 102 that operation of the collection andreturning pump 100 is not stopped (step S12: NO), the processing fromstep S10 and thereafter is performed.

In the case it is determined by the control unit 102 that operation ofthe collection and returning pump 100 has been stopped (step S12: YES),then in step S13, the control unit 102 determines whether or not it isimmediately after the collection operation.

In the case it is determined by the control unit 102 that it isimmediately after the collection operation (step S13: YES), the controlunit 102 opens the clamps 72 b and 72 c (see FIG. 14). Consequently, theinner hole of the first applied load measurement unit 60 and the innerhole of the second applied load measurement unit 62 are placed incommunication with each other. At this time, the internal pressure ofthe first applied load measurement unit 60 and the internal pressure ofthe second applied load measurement unit 62 both have the same pressure.The control unit 102 may also open the clamp 72 a.

In addition, in the first internal pressure calculation step of stepS15, the first internal pressure calculation unit 112 calculates theinternal pressure of the first applied load measurement unit 60 on thebasis of the load detected by the first load detecting unit 88 and thecalibration curve La, the slope of which has been corrected. Further, inthe second internal pressure calculation step of step S16, the secondinternal pressure calculation unit 114 calculates the internal pressureof the second applied load measurement unit 62 on the basis of the loaddetected by the second load detecting unit 90.

Subsequently, in the correction step of step S17, the estimated data Bis corrected in a manner so that the internal pressure calculated by thefirst internal pressure calculation unit 112 becomes equivalent to theinternal pressure calculated by the second internal pressure calculationunit 114 (see FIG. 15). The corrected estimated data Ba is saved(stored) in the storage unit 104. Thereafter, the processing from stepS9 and thereafter is performed.

In step S13, in the case it is determined by the control unit 102 thatit is not immediately after the collection operation (that it isimmediately after the returning operation) (step S13: NO), then in stepS18, the control unit 102 determines whether or not the blood collectionoperation has ended. More specifically, in the event that the collectionoperation and the returning operation cycles have been performed apredetermined number of times, the control unit 102 determines that thecollection of blood components has ended.

If it is determined by the control unit 102 that the collection of bloodcomponents is not ended (that collection of blood components is takingplace) (step S18: NO), the processing from step S15 and thereafter isperformed. In this case, since it is immediately after the returningoperation and thus the clamps 72 b and 72 c are already open (see FIG.8), the process of step S14 need not necessarily be performed. Moreover,the control unit 102 may open the clamp 72 a before performing theprocess of step S15.

In the case it is determined by the control unit 102 that the collectionof blood components has ended (step S18: YES), the current execution ofthe flowchart is brought to an end.

In this case, the blood component collection system 10 and the circuitinternal pressure acquisition method according to the present embodimentexhibit the following effects.

During blood component collection (during a blood collection operationor during a blood returning operation), in the case that the collectionand returning pump 100 is in operation, a load is detected by the firstload detecting unit 88, which is the sum of the internal pressure(circuit internal pressure) of the blood collection line 42 a throughwhich the blood flows, and the reaction force of the first applied loadmeasurement unit 60 (the restorative force accompanying deformation ofthe first applied load measurement unit 60). That is, in the case thatthe circuit internal pressure is a positive pressure, as shown in FIG.16A, the load detected by the first load detecting unit 88 (the pressingforce from the first applied load measurement unit 60) is obtainedsimply by adding the circuit internal pressure and the reaction force.On the other hand, in the case that the circuit internal pressure is anegative pressure, as shown in FIG. 16B, the load detected by the firstload detecting unit 88 is obtained simply by subtracting the absolutevalue of the circuit internal pressure from the reaction force.

However, as shown in FIG. 17, the reaction force of the first appliedload measurement unit 60 decreases over time. In FIG. 17, an image isshown of a temporal change in the reaction force of the first appliedload measurement unit 60, in the case that the reaction force of thefirst applied load measurement unit 60 when the cassette 28 is mountedin the cassette mounting unit 78 is set to zero. The reason that thereaction force of the first applied load measurement unit 60 decreasesover time in the foregoing manner is due to the fact that creep isgenerated accompanying continuation of a state in which the firstapplied load measurement unit 60 is pressed by the first load detectingunit 88. Accordingly, when a fixed value that does not change over timeis used as the reaction force of the first applied load measurement unit60, the measurement accuracy of the internal pressure of the firstapplied load measurement unit 60 is lowered.

Thus, the blood component collection system 10 is equipped with the dataacquisition unit 106, the estimated data calculation unit 108, thereaction force calculation unit 110, and the first internal pressurecalculation unit 112. In addition, before collection of blood componentsis carried out in the cassette attached state, the data acquisition unit106 acquires the initial data A which is indicative of the temporalchange in the reaction force of the first applied load measurement unit60. On the basis of the initial data A, the estimated data calculationunit 108 calculates the estimated data B for the purpose of estimatingthe reaction force of the first applied load measurement unit 60 duringcollection of the blood components.

During collection of the blood components, the reaction forcecalculation unit 110 calculates the reaction force of the first appliedload measurement unit 60 based on the estimated data B. The firstinternal pressure calculation unit 112 calculates the internal pressure(circuit internal pressure) of the first applied load measurement unit60 on the basis of the reaction force calculated by the reaction forcecalculation unit 110, and the load detected by the first load detectingunit 88. Consequently, since based on the estimated data B it ispossible to calculate in real time the reaction force of the firstapplied load measurement unit 60 during collection of the bloodcomponents, which changes with the passage of time, it is possible forthe circuit internal pressure to be accurately measured. The circuitinternal pressure, for example, ranges from −300 mmHg to 500 mmHg.

In this case, the estimated data B is calculated by using the initialdata A. Therefore, as time elapses, there is a possibility that thereaction force calculated using the estimated data B may deviate fromthe actual reaction force of the first applied load measurement unit 60.However, the blood component collection system 10 includes thecorrection unit 116 that corrects the estimated data B in a manner sothat the internal pressure calculated by the first internal pressurecalculation unit 112 becomes equivalent to the internal pressurecalculated by the second internal pressure calculation unit 114, at atime between the collection operation and the returning operation, in astate in which the inner hole of the first applied load measurement unit60 and the inner hole of the second applied load measurement unit 62communicate with each other and the collection and returning pump 100 isstopped.

In this instance, since the second applied load measurement unit 62 ismore easily deformed than the first applied load measurement unit 60,the relationship between the load detected by the second load detectingunit 90 and the pressure corresponding to the load is extremely stable.Stated otherwise, the second applied load measurement unit 62 is lesslikely to undergo creep deformation than the first applied loadmeasurement unit 60. Therefore, the second internal pressure calculationunit 114 is capable of calculating relatively accurately the internalpressure (positive pressure) of the second applied load measurement unit62. On the other hand, the first internal pressure calculation unit 112is capable of calculating the internal pressure (positive pressure andnegative pressure) of the first applied load measurement unit 60.

Additionally, since the estimated data B is corrected in a manner sothat the internal pressure calculated by the first internal pressurecalculation unit 112 becomes equivalent to the internal pressurecalculated by the second internal pressure calculation unit 114, thereaction force calculated using the estimated data B can be preventedfrom deviating from the actual reaction force of the first applied loadmeasurement unit 60 as time elapses. Thus, the circuit internal pressurecan be measured more accurately.

The correction unit 116 corrects the estimated data B each time that thecollection operation and the returning operation are switched.Consequently, it is possible to accurately measure the circuit internalpressure over the entire period of collection of biological liquidcomponents (collection of blood components).

Immediately after the biological component collection device (cassette28) is mounted in the separation device (centrifugal separation device14), the applied load measurement unit (first applied load measurementunit 60) undergoes creep deformation to a comparatively large extent,and therefore, the reaction force of the applied load measurement unit(first applied load measurement unit 60) easily fluctuates. However, thedata acquisition unit 106 acquires the initial data A during thepredetermined data acquisition time period t2 after the elapse of thepredetermined time period t1 from when the biological componentcollection device (cassette 28) was mounted in the separation device(centrifugal separation device 14). Therefore, the accuracy of theestimated data B can be improved.

The estimated data calculation unit 108 calculates the estimated data Busing a least squares method based on the initial data A. Consequently,it is possible to easily calculate the estimated data B.

The biological component collection device is not limited to being inthe form of the cassette 28. Accordingly, the biological componentcollection device may be equipped with a first soft tube member havingthe blood collection line 42 a, and a second soft tube member having theblood returning line 42 b, and may be constituted in a manner so thatboth end portions of the first soft tube member and the second soft tubemember are connected together respectively via connectors.

The internal pressure calculation data which is used when calculatingthe circuit internal pressure using the load detected by the first loaddetecting unit 88 is not limited to the calibration curve L, but may bea table that is prepared beforehand. The first load detecting unit 88and the second load detecting unit 90 may be configured in a manner soas to measure the load (in a non-contact manner) without applyingpressure to the first applied load measurement unit 60 and the secondapplied load measurement unit 62.

The scope of application of the present invention is not limited to ablood component collection system 10, but may be applied to varioussystems through which a liquid is made to flow through a flow path, forexample, a whole blood donation system, or a culture apparatus forvarious types of cells which are collected or cultured from patients ordonors, or alternatively, a medicinal solution administration system, orthe like. Accordingly, the liquid that flows in the biological componentcollection device (biological component collection system) is notlimited to blood.

The biological component collection system and the circuit internalpressure acquisition method according to the present invention are notlimited to the above-described embodiments, and it goes without sayingthat various modifications could be adopted therein within a range thatdoes not depart from the essence and gist of the present invention.

DESCRIPTION OF REFERENCE CHARACTERS

-   10 . . . blood component collection system (biological component    collection system)-   14 . . . centrifugal separation device (separation device)-   28 . . . blood component collection cassette (biological component    collection device)-   42 . . . blood line (biological liquid line)-   53 . . . line forming member-   60 . . . first applied load measurement unit-   62 . . . second applied load measurement unit-   88 . . . first load detecting unit-   90 . . . second load detecting unit-   106 . . . data acquisition unit-   108 . . . estimated data calculation unit-   110 . . . reaction force calculation unit-   112 . . . first internal pressure calculation unit-   114 . . . second internal pressure calculation unit-   116 . . . correction unit-   A . . . initial data-   B, Ba . . . estimated data

The invention claimed is:
 1. A circuit internal pressure acquisitionmethod using a biological component collection system equipped with aseparation device adapted to separate a biological component from abiological liquid, a biological component collection device configuredto be attachable to the separation device and having a biological liquidline formed therein through which the biological liquid or thebiological component flows, and a collection and returning pump, thebiological component collection system performing a collection operationfor collecting a desired biological component in the biological liquidby allowing the biological liquid to flow from a donor through thebiological liquid line to the separation device under an action of thecollection and returning pump, and a returning operation for returningremaining biological components to the donor from the separation devicethrough the biological liquid line under the action of the collectionand returning pump; wherein the biological component collection deviceis formed of a soft material and has a line forming member defining thebiological liquid line; the separation device comprising: a first loaddetecting unit adapted to detect a load applied to a first applied loadmeasurement unit which partially makes up the line forming member in anattached state in which the biological component collection device isattached to the separation device; and a second load detecting unitadapted to detect a load applied to a second applied load measurementunit which partially makes up the line forming member in the deviceinstalled state; the circuit internal pressure acquisition methodcomprising: a data acquisition step of acquiring, before the biologicalliquid or the biological component is made to flow through thebiological liquid line for biological component collection, initial dataindicative of a timewise change in a reaction force of the first appliedload measurement unit using the load detected by the first loaddetecting unit in the device installed state; an estimated datacalculation step of calculating on the basis of initial data, estimateddata for estimating the reaction force of the first applied loadmeasurement unit which changes depending on time during collection ofthe biological component; a reaction force calculation step ofcalculating, during collection of the biological component, the reactionforce on the basis of the estimated data; a first internal pressurecalculation step of calculating an internal pressure of the firstapplied load measurement unit on the basis of the reaction forcecalculated in the reaction force calculation step and the load detectedby the first load detecting unit; a second internal pressure calculationstep of calculating an internal pressure of the second applied loadmeasurement unit on the basis of the load detected by the second loaddetecting unit; and a correction step of correcting the estimated datain a manner so that the internal pressure calculated in the firstinternal pressure calculation step becomes equivalent to the internalpressure calculated in the second internal pressure calculation step, ata time between the collection operation and the returning operation, andin a state in which the collection and returning pump is stopped.
 2. Thecircuit internal pressure acquisition method according to claim 1,wherein the separation device further comprises a correction unit andwherein the correction unit corrects the estimated data each time thatthe collection operation and the returning operation are switched. 3.The circuit internal pressure acquisition method according to claim 2,wherein the separation device further comprises a data acquisition unitand wherein the data acquisition unit acquires the initial data during apredetermined data acquisition time period, after a predetermined timeperiod has elapsed from when the biological component collection devicewas mounted in the separation device.
 4. The circuit internal pressureacquisition method according to claim 3, wherein the separation devicefurther comprises an estimated data unit and wherein the estimated dataunit calculates the estimated data using a least squares method based onthe initial data.
 5. The circuit internal pressure acquisition methodaccording to claim 1, wherein the separation device further comprises adata acquisition unit and wherein the data acquisition unit acquires theinitial data during a predetermined data acquisition time period, aftera predetermined time period has elapsed from when the biologicalcomponent collection device was mounted in the separation device.
 6. Thecircuit internal pressure acquisition method according to claim 5,wherein the separation device further comprises an estimated datacalculation unit and wherein the estimated data calculation unitcalculates the estimated data using a least squares method based on theinitial data.
 7. The circuit internal pressure acquisition methodaccording to claims 1, wherein the separation device further comprisesan estimated data calculation unit and wherein the estimated datacalculation unit calculates the estimated data using a least squaresmethod based on the initial data.